DESCRIPTION: (Applicant's Description) Prostate cancer has become the most common cancer affecting men in this country. Androgen has been proposed to be a risk factor promoting the progression of prostate epithiums from latent carcinomas to invasive cancers. Androgen stimulation of prostate cancer cell growth is associated with a decrease in cellular prostatic acid phosphatase (PAcP) activity, the major protein tyrosine phosphatase in the cells. The expression of a putative cellular form of PAcP driven by a complement dioxyribonucleic acid (cDNA) expression vector correlates with a diminished growth rate. The regulation of tyrosine phosphorylation is an important process in cell proliferation, we therefore propose that androgen-responsive cellular PAcP ultimately plays an important role in cell growth regulation of prostate epitheliums and be involved in cancer progression. The approach in this proposal is to delineate the regulatory mechanism of phosphotyrosine (p-tyr) dephosphorylation by cellular PAcP. The working hypothesis is that the understanding of p-tyr dephosphorylation by androgen- responsive PAcP will lead us to understand one mechanism of androgen effects in the multistage prostate malignant transformation. In order to test this working hypothesis directly, the following specific aims will be accomplished. We will transfect several different cells with a PAcP cDNA expression vector to examine the cell growth regulation possibly by cellular PAcP expression. Cell growth regulation by PAcP will be further studied by transfecting cells with PAcP cDNA in an inducible expression vector and compare the biological effects of PAcP expression in the presence or absence of inducing agents. The mechanism of PAcP regulation on the cellular growth will be investigated by identifying its putative substrate phosphoprotein(s) that has a decreased p-tyr level in PAcP- expressing cells. The effect of cellular PAcP expression on the tumor development in nude mice will be examined by injecting PAcP cDNA- transfected cells subcutaneously. The results from these proposal experiments will lead to our long term goal in understanding the mechanisms of multistage prostate malignant transformation for improving the prevention and the therapy of the disease.